A genetic disorder, or genetic disease is a disease caused by abnormal expression of one or more genes in a person causing a clinical phenotype. There are a number of possible causes for genetic defects:

Defective genes are often inherited from the parents. In this case, the genetic disorder is known as a hereditary disease. This can often happen unexpectedly when two healthy carriers of a defective recessive gene reproduce, but can also happen when the defective gene is dominant.

Currently around 4,000 genetic disorders are known; new ones are constantly discovered. The vast majority of these disorders are quite rare, and affect one person in every several thousands or millions. Cystic fibrosis is the most common genetic disorder; around 5% of the population of the United States carry the defective gene.

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A number of genetic disorders are due to the change of a single gene, resulting in an enzyme or other protein not being produced or having altered functionality, they are called monogenic disorders. The change can be trivial and relatively harmless in its effects, such as color blindness, or lethal such as Tay-Sachs. Other disorders, though harmful to those afflicted with them, appear to offer some advantage to carriers; as in carriers of sickle cell anemia and thalassemia appearing to have enhanced resistance to malaria. Several hereditary diseases are sex-linked, meaning that they afflict one sex much more common than the other because the mutation is located on the X (or, rarely, on the Y) chromosome.

Where genetic disorders are the result of a single mutated gene they can be passed on to subsequent generations in the following ways, however genomic imprinting and uniparental disomy may affect inheritance patterns. The divisions between recessive and dominant are not "hard and fast" although the divisions between autosomal and X-linked are (related to the position of the gene). For example, achondroplasia is typically considered a dominant disorder, but kids with two genes for achondroplasia have a severe skeletal disorder that achondroplasics could be viewed as carriers of. Sickle-cell anemia is also considered a recessive condition, but carriers of it have increased immunity to malaria in early childhood, which could be described as a dominant condition.

Inheritance pattern

Description

Examples

Autosomal dominant

Only one mutated copy of the gene is needed for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. There is a 50% chance that a child will inherit the mutated gene.

Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Two unaffected people who each carry one copy of the mutated gene have a 25% chance with each pregnancy of having a child affected by the disorder.

X-linked dominant disorders are caused by mutations in genes on the X chromosome. Only a few disorders have this inheritance pattern. Females are more frequently affected than males, and the chance of passing on an X-linked dominant disorder differs between men and women. The sons of a man with an X-linked dominant disorder will not be affected, and his daughters will all inherit the condition. A woman with an X-linked dominant disorder has a 50% chance of having an affected daughter or son with each pregnancy. Some X-linked dominant conditions, such as Aicardi Syndrome, are fatal to boys, therefore only girls have them (and boys with Klinefelter Syndrome).

X-linked recessive disorders are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene. With each pregnancy, a woman who carries an X-linked recessive disorder has a 50% chance of having sons who are affected and a 50% chance of having daughters who carry one copy of the mutated gene.

Y-linked disorders are caused by mutations on the Y chromosome. Only males can get them, and all of the sons of an affected father are affected. Since the Y chromosome is very small, Y-linked disorders only cause infertility, and may be circumvented with the help of some fertility treatments.

This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Because only egg cells contribute mitochondria to the developing embryo, only females can pass on mitochondrial conditions to their children.

Genetic disorders may also be complex, multifactorial or polygenic, this means that they are likely associated with the effects of multiple genes in combination with lifestyle and environmental factors. Multifactoral disorders include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified.

Changes that affect entire chromosomes or segments of chromosomes can cause problems with growth, development, and function of the body's systems. These changes can affect many genes along the chromosome and alter the proteins made by those genes. Conditions caused by a change in the number or structure of chromosomes are known as chromosomal disorders.

Some chromosomal conditions are caused by changes in the number of chromosomes, called aneuploidy. These changes are not inherited, but occur as random events during the formation of reproductive cells (ova and sperm cells). An error in cell division called nondisjunction results in reproductive cells with an abnormal number of chromosomes. For example, a reproductive cell may accidentally gain or lose one copy of a chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra (trisomy) or missing chromosome (monosomy) in each of the body’s cells. The formation of ring chromosomes following fertilization also cause genetic disorders.

Chromosomal disorders can also be caused by chromosome structure. These changes are caused by the breakage and reunion of chromosome segments when an egg or sperm cell is formed or in early fetal development. Pieces of DNA can be rearranged within one chromosome, or transferred between two or more chromosomes. The effects of structural changes depend on their size and location. Many different structural changes are possible; some cause medical problems, while others may have no effect on a person’s health.

Although it is possible to inherit some types of chromosomal abnormalities, most chromosomal disorders are not passed from one generation to the next.

Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with the effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified.

On a pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns as with Mendelian diseases. But this does not mean that the genes cannot eventually be located and studied. There is also a strong environmental component to many of them (e.g., blood pressure).

Genetic disorders rarely have effective treatments, though gene therapy is being tested as a possible treatment for some genetic diseases, including some forms of retinitis pigmentosa[1]

Gauchers disease is a genetic disease affecting metabolism. It is more treatable than most other genetic diseases, and can be treated with enzyme replacement therapy, medication (miglustat and imiglucerase), and bone marrow transplantion.[2]